Over 70% of all birth defects in humans affect the head and face. Cleft lip with or without cleft palate (CLP) is one of the most common of these defects, occurring in approximately 1 per 1,000 live births. Children with CLP suffer deficits in speech, hearing and cognition and have higher morbidity and mortality throughout life compared to their unaffected contemporaries. Despite its frequency and clinical importance, little is known about the etiology of CLP , and there are currently no strategies for reducing its prevalence. Because of this, the identification of risk factors for CLP is part of the National Institute of Dental and Craniofacial Research (NIDCR) Strategic Plan for 2009-2013. Suspected CLP risk factors that have not been fully explored include environmental toxicants. An important group of toxicants, as defined by the U.S. Environmental Protection Agency (EPA), are hazardous air pollutants, or HAPs (e.g., benzene, diesel particulate matter). HAPs are important potential risk factors for several reasons, including: 1) they are known or suspected to cause a range of adverse health outcomes; 2) the potential for exposure is increasing in many communities throughout the U.S.; and 3) there are currently no national air quality standards as there are for other air pollutants (e.g., ozone). Although there is evidence from occupational studies that maternal exposure to certain HAPs is associated with CLP, the teratogenic potential of environmental concentrations of HAPs (which are lower than in occupational settings but a more common source of exposure) has not been assessed. It is important to examine the association between maternal exposure HAPs and CLP risk, as all women, in varying degrees, are exposed to HAPs during pregnancy. Furthermore, the developing embryo appears to be particularly vulnerable to the effects of HAPs. The investigators will examine the role of on CLP risk using a novel application of Bayesian hierarchical modeling, which accounts for census tract-level data, exposure assessment confidence and multiple pollutants. Data on study subjects will be obtained from the Texas Birth Defects Registry; one of the largest population-based, active surveillance systems of birth defects in the world. Exposure to HAPs will be determined using the U.S. EPA National-Scale Air Toxics Assessment. The proposed study builds on 1) the exceptional resources provided by the Texas Birth Defects Registry, which includes data on approximately 2,500 nonsyndromic, isolated CLP cases, 2) a large comparison group including all unaffected births in Texas, 3) the extensive HAP exposure assessment conducted by the U.S. EPA, 4) the principal investigator's expertise in birth defects epidemiology and 5) a strong group of research collaborators. This study is expected to identify those HAPs that deserve further exploration in independent populations, while resulting in a novel method for assessing these and other environmental toxicants. Ultimately, the identification of CLP risk factors will open the door to new strategies for lowering the prevalence of these significant conditions.